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1.
Acta Biomater ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31926335

RESUMO

Targeting delivery of photosensitizers to mitochondria as the most sensitive cellular organelles to reactive oxygen species (ROS) by positively charged polymeric nanocarriers (NCs) is one of the useful methods for efficient photodynamic therapy (PDT). However, the NCs with positively charged mitochondria-targeting moieties are easily cleaned during circulation, restricting their in vivo applications. Herein, to address this issue and enhance in vivo PDT efficacy, we developed a sequential-targeting delivery system consisting of mitochondria-targeting micelles as the core prepared from the cationic amphiphilic copolymer for loading chlorin e6 (Ce6) and a tumor-targeting pH-dependent charge transformational layer as the shell obtained from 2,3-dimethylmaleic anhydride modified Biotin-PEG4000-NH2 (BioPEGDMA) via electrostatic interaction. Concealed by the anionic shell, the as-prepared NCs showed longer retention within the first stage of tumor-targeting. Then, the accumulated NCs conversed to positive charge in tumor extracellular microenvironment (pH ∼ 6.5), which could be more effectively internalized by tumor cells, and the re-exposed triphenylphosphonium (TPP) groups endowed their second-stage targetability to the mitochondria. In vivo experiments revealed that the Ce6-loaded NCs exhibited remarkable tumor inhibition rates of 84.1% and 93.2% on BALB/c nude mice and Kunming mice, respectively, under 660 nm NIR irradiation, and stimulated immune responses with upregulated expression of IFN-γ, TNF-α and CD3+ in tumor tissues, and enhanced activation of CD3+/CD4+, CD3+/CD8+ T lymphocytes and DCs in both tumor tissues and lymph glands. This work provided a new pathway for the development of smart drug delivery system with advanced PDT efficacy. Statement of significance Although the existing targeting delivery of photosensitizers to mitochondria by positively charged nanocarriers (NCs) have efficiently enhanced photodynamic therapy (PDT), their positive charges caused rapid clearance during circulation, which has restricted their in vivo applications. Therefore, we fabricated a novel sequential-targeting NC to solve the problem. The tumor accumulated NCs conversed to positive charge in tumor extracellular microenvironment, and the re-exposed triphenylphosphonium groups initiated second-stage targetability to mitochondria. This system exhibited remarkable tumor inhibition efficiency both in vitro and in vivo. Moreover, as we hypothesized, mitochondria-located PDT could promote immune response, resulting in improvement of PDT. The strategy of sequential targeting-based PDT in combination with augmented immune response showed a novel pathway for the development of smart drug delivery system with advanced PDT.

2.
Langmuir ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31885276

RESUMO

Because of the unique optical properties of gold nanomaterials, the preparation of gold nanomaterials with excellent chirality has received extensive attention. In order to develop a simple fabrication method for three-dimensional chiral Au nanostructures with a size of several hundred nanometers, chiral gold nanoparticles were developed to transfer chirality of a peptide to gold nanoparticles. In this study, the controlled synthesis of asymmetric gold nanopolyhedrons was achieved. The asymmetric gold nanopolyhedrons prepared via peptide-directed growth can exhibit strong circular dichroism (∼±50 mdeg) couplets in the visible range (500-600 nm). Also, the morphology of chiral Au nanododecahedrons-peptide particles showed distorted and asymmetric properties. In order to prove that the size and spatial structure of gold nanopolyhedrons have an influence on their chiral optical properties, Au nanotrioctahedron-peptide particles were prepared by using Au nanotrioctahedrons with different morphologies. Au nanotrioctahedron-peptide particles also exhibited circular dichromatic couplets in the visible region.

3.
Front Chem ; 7: 370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192192

RESUMO

Thin film coating of charged nanoparticles with oppositely charged polymers is an efficient and straightforward way for surface modification, but synthetic polyelectrolytes should be replaced by abundant biopolymers. In this study a thin film of chitosan was adsorbed onto colloidal lignin particles (CLPs) that were then systematically studied for olive oil stabilization with an objective to develop shape-retaining microcapsules that comprised of only renewable biomaterials. Full surface coverage was achieved with merely 5 wt% of chitosan relative to the dry weight of CLPs, reversing their surface charge from negative to positive. Such modification rendered the chitosan-coated particles excellent stabilizers for forming Pickering emulsions with olive oil. The emulsion droplets could be further stabilized by sodium triphosphate that provided ionic intra- and inter-particle cross-linking of the chitosan corona on the CLPs. Following the optimum conditions, the non-cross-linked microcapsules exhibited a strong stability against coalescence and the electrostatically stabilized ones additionally retained their shape upon drying and rewetting. Non-cross-linked microcapsules were used to demonstrate encapsulation and rapid release of ciprofloxacin as a model lipophilic drug in aqueous media. Overall, the combination of antimicrobial chitosan and antioxidative lignin nanoparticles hold unprecedented opportunities as biocompatible and biodegradable materials for controlled drug delivery.

4.
Biotechnol Biofuels ; 12: 148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223338

RESUMO

Background: Microbial lipids derived from various lignocellulosic feedstocks have emerged as a promising candidate for the biodiesel industry and a potential substitute for high value-added fats. However, lignocellulosic biomass, especially herbaceous biomass, such as water hyacinth, contains high concentrations of nitrogenous components. These compounds impede microbial lipid production, as lipid biosynthesis is commonly induced by imposing a nutrient deficiency, especially nitrogen starvation. Novel strategies and bioprocesses are pivotal for promoting lipid production from nitrogen-rich biomass. Results: Here a combined strategy of phosphate removal and acetate supplementation was described for enhanced microbial lipid production on water hyacinth hydrolysates by Cutaneotrichosporon oleaginosum (formerly Cryptococcus curvatus). Lipid production was significantly improved, when the phosphorus limitation and sugars/acetate co-utilization strategies were used separately. In this case, acetate and glucose were consumed simultaneously. Lipid production was observed by the combination of phosphate removal with acetate supplementation. Lipid titer, content, and yield were determined to be 7.3 g/L, 59.7% and 10.1 g/100 g raw water hyacinth, respectively. These data were increased by 4.2, 4.6, and 4.3 times, respectively, compared to those from the unprocessed hydrolysates. The fatty acid compositions of the resulting lipids bear a marked resemblance to those of rapeseed oil, indicating their applicability to the biodiesel industry. Conclusions: The combination of phosphate removal and acetate supplementation was successful in significantly enhancing microbial lipid production. This strategy offers a valuable solution for nitrogen-rich lignocellulosic feedstocks utilization, which should foster more economical nitrogen-rich biomass-to-lipid bioprocesses.

5.
Mater Sci Eng C Mater Biol Appl ; 98: 737-745, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813078

RESUMO

Controlled release of incorporated foreign DNA from multilayered films plays an important role in surface-mediated gene delivery. Herein, multilayered polyelectrolyte complex thin films, composed of dendrimer-grafted bio-reducible cationic poly(disulfide amine) and plasmid DNA, were fabricated via layer-by-layer (LBL) assembly for in vitro localized gene delivery. The UV absorbance and thickness of the LBL films were found to have linear correlation with the numbers of poly(disulfide amine)/DNA bilayers. Although LBL films were stable in PBS buffer, their degradation could be triggered by reducing agents (i.e. glutathione, GSH). The degradation rate of the films is directly proportional to the GSH concentration, which in turn affected the corresponding gene expression. All poly(disulfide amine)/DNA films exhibited lower cytotoxicity and higher transfection activity in comparison with PEI/DNA multilayered films. Moreover, LBL films showed the highest transfection efficiency in the presence of 2.5 mM GSH when cultured with 293T cells, with ~36% GFP-positive 293T cells after 5-days of co-culture. These DNA-containing reducible films could potentially be useful in gene therapy and tissue engineering by controlling the release of incorporated DNA.


Assuntos
DNA/química , Dendrímeros/química , Poliaminas/química , Polímeros/química , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Células HEK293 , Humanos , Poliaminas/efeitos adversos , Polímeros/efeitos adversos
6.
Cancer Res ; 79(6): 1038-1040, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30877100

RESUMO

Circulating tumor DNA (ctDNA) holds great promise as a noninvasive diagnostic tool to guide treatment for patients with lung cancer. Two studies by Phallen and colleagues and Anagnostou and colleagues correlated sensitive measures of ctDNA with clinical responses to tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors, respectively, in patients with non-small cell lung cancer (NSCLC). Together, these studies further highlight the potential clinical utility of serial ctDNA monitoring in patients with NSCLC undergoing treatment with both targeted therapies and immunotherapies.See related articles by Phallen et al., p. 1204, and Anagnostou et al., p. 1214.

7.
Colloids Surf B Biointerfaces ; 178: 263-268, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877911

RESUMO

Ammonium bicarbonate (ABC) liposomes can only release drugs extracellularly while intracellular drug delivery could be more promising than extracellular release in chemotherapy. The purpose of this work was to endow the ABC liposomes with tumor-triggered targeting effect, to realize the intracellular drug release and retain the long circulation characteristics of the liposomes. The tumor-triggered targeting ABC (TT-ABC) liposomes were proposed to improve uptake of tumor cells owing to folate (FA) - specific binding. To retain the long circulation characteristics of the TT-ABC liposomes, we synthesized PEGylated phospholipid with a pH-sensitive imine bond (DSPE-PEG5000) and added it to the liposomes. After endocytosis by tumor cells via active targeting, the TT-ABC liposomes produced carbon dioxide (CO2) bubbles at elevated temperature or in the acidic endo/lysosome. The permeable defects could be created in the phospholipid bilayer by the generating CO2 bubbles, so the liposomes could quickly release the drugs intracellularly. Doxorubicin (DOX) loaded TT-ABC (DOX@TT-ABC) liposomes exhibited good stability at physiological pH (7.4) and released DOX quickly at reduced pH (6.4) and hyperthermia (42 °C). DOX@TT-ABC liposomes showed significantly enhanced cellular uptake, intracellular accumulation of DOX, and cytotoxicity at pH 6.4 and 42 °C.


Assuntos
Bicarbonatos/química , Doxorrubicina/química , Lipossomos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Concentração de Íons de Hidrogênio , Bicamadas Lipídicas/química
8.
Int J Biol Macromol ; 130: 615-621, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30831169

RESUMO

A series of amphiphilic chitin derivatives were synthesized by conjugating hexadecyl groups (degree of substitute of hexadecyl groups (DSH) = 0.11, 0.18, and 0.24) onto the backbone of quaternized chitins (degree of substitute of quaternary ammonium groups (DSQ) = 0.36). The amphiphilic chitin derivatives could self-assemble into cationic micelles with hydrophobic alkyl side chain as core and hydrophilic quaternary ammonium groups as shell in deionized water. The biocompatible cationic micelles with an average particle size of 332.4-385.0 nm showed a drug loading content (DLC) of 10.2%-15.1%. The release behavior of DOX from micelles strongly depended on the DSH values of chitin derivatives. DOX-loaded micelles effectively inhibited the growth of HepG2 cells through being internalized into HepG2 cells, and releasing DOX into the cytoplasm and nucleus. This work presented a novel chitin-based nanocarrier for potential chemotherapy.


Assuntos
Quitina , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Micelas , Tensoativos , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Quitina/química , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Análise Espectral , Tensoativos/química
9.
Nat Commun ; 10(1): 589, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718483

RESUMO

Artificial heterostructures composed of dissimilar transition metal oxides provide unprecedented opportunities to create remarkable physical phenomena. Here, we report a means to deliberately control the orbital polarization in LaNiO3 (LNO) through interfacing with SrCuO2 (SCO), which has an infinite-layer structure for CuO2. Dimensional control of SCO results in a planar-type (P-SCO) to chain-type (C-SCO) structure transition depending on the SCO thickness. This transition is exploited to induce either a NiO5 pyramidal or a NiO6 octahedral structure at the SCO/LNO interface. Consequently, a large change in the Ni d orbital occupation up to ~30% is achieved in P-SCO/LNO superlattices, whereas the Ni eg orbital splitting is negligible in C-SCO/LNO superlattices. The engineered oxygen coordination triggers a metal-to-insulator transition in SCO/LNO superlattices. Our results demonstrate that interfacial oxygen coordination engineering provides an effective means to manipulate the orbital configuration and associated physical properties, paving a pathway towards the advancement of oxide electronics.

10.
J Telemed Telecare ; 25(2): 80-92, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29172929

RESUMO

BACKGROUND: Most patients with chronic kidney disease (CKD) fail to achieve blood pressure (BP) management as recommended. Meanwhile, the effects of promising intervention and telehealth on BP control in CKD patients remain unclear. We aimed to evaluate the efficacy of telehealth for BP in CKD non-dialysis patients. METHODS: Databases including MEDLINE, EMBASE, CENTRAL, CNKI, Wanfang, VIP and CBM were systematically searched for randomised controlled trials or quasi-randomised controlled trials on telehealth for BP control of CKD3-5 non-dialysis patients. We analysed systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), serum creatinine, and estimated glomerular filtration rate (eGFR) with a fixed-effects model. RESULTS: Three studies, with total 680 subjects, were included in our systematic review and two were included for meta-analysis. Pooled estimates showed decreased SBP (pooled mean difference (MD), -5.10; 95% confidence interval (CI), -11.34, 1.14; p > 0.05, p = 0.11), increased DBP (pooled MD, 0.45; 95% CI, -4.24, 5.13; p > 0.05, p = 0.85), decreased serum creatinine (pooled MD, -0.38; 95% CI, -0.83, 0.07; p > 0.05, p = 0.10) and maintained eGFR (pooled MD, 4.72; 95% CI, -1.85, 11.29; p > 0.05, p = 0.16) in the telehealth group. There was no significant difference from the control group. MAP (MD, 0.6; 95% CI, -6.61, 7.81; p > 0.05, p = 0.87) and BP control rate ( p > 0.05, p = 0.8), respectively, shown in two studies also demonstrated no statistical significance in the telehealth group. CONCLUSIONS: There was no statistically significant evidence to support the superiority of telehealth for BP management in CKD patients. This suggests further studies with improved study design and optimised intervention are needed in the future.


Assuntos
Hipertensão/epidemiologia , Hipertensão/terapia , Insuficiência Renal Crônica/epidemiologia , Telemedicina/organização & administração , Pressão Sanguínea , Creatinina/sangue , Taxa de Filtração Glomerular , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal
11.
Biomacromolecules ; 20(2): 693-704, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30358992

RESUMO

Brittleness has hindered commercialization of cellulose nanofibril (CNF) films. The use of synthetic polymers and plasticizers is a known detour that impairs biodegradability and carbon footprint of the product. Herein, we utilize a variety of softwood Kraft lignin morphologies to obtain strong and ductile CNF nanocomposite films. An optimum 10 wt % content of colloidal lignin particles (CLPs) produced films with nearly double the toughness compared to a CNF film without lignin. CLPs rendered the films waterproof, provided antioxidant activity and UV-shielding with better visible light transmittance than obtained with irregular lignin aggregates. We conclude based on electron microscopy, dynamic water sorption analysis, and tp-DSC that homogeneously distributed CLPs act as ball bearing lubricating and stress transferring agents in the CNF matrix. Overall, our results open new avenues for the utilization of lignin nanoparticles in biopolymer composites equipped with versatile functionalities for applications in food packaging, water purification, and biomedicine.

12.
Colloids Surf B Biointerfaces ; 175: 248-255, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30540972

RESUMO

To realize efficiently cellular uptake and enhance the immunostimulation, thiolated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) were self-assembled on hollow gold nanospheres (HGNs) to form CpG-HGNs. The cellular uptake of CpG-HGNs in immune cells was studied in RAW 264.7 cells. Due to the enhanced delivery efficiency, CpG-HGNs exhibited a higher immune stimulatory activity compared with CpG ODNs, resulting in a dramatically enhanced secretion of proinflammatory cytokines. In addition, CpG-HGNs showed low cytotoxicity in RAW 264.7 cells. CpG-HGNs could potentially realize synergistic photothermal therapy and immunotherapy in vivo.


Assuntos
Ouro/química , Nanosferas/química , Oligodesoxirribonucleotídeos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lasers , Camundongos , Microscopia Eletrônica de Transmissão , Nanosferas/administração & dosagem , Nanosferas/ultraestrutura , Neoplasias/metabolismo , Neoplasias/terapia , Células RAW 264.7 , Temperatura Ambiente
13.
Biomed Pharmacother ; 109: 1276-1286, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551378

RESUMO

Type 2 diabetes mellitus (T2DM) is a chronic degenerative endocrine and metabolic disease with high mortality and morbidity, yet lacks effective therapeutics. We recently generated a novel fusion peptide INSR-IgG4Fc, Yiminsu (YMS), to facilitate the high-affinity binding and transportation of insulin. Thus, the aim of the present study was to determine whether the novel recombinant peptide, YMS, could contribute to restoring insulin sensitivity and glycaemic control in insulin resistance models and revealing its underlying mechanism. Palmitic acid (PA)-treated LO2 cells and high fat diet (HFD)-fed mice were treated with YMS. Therapeutic effects of YMS were measured using Western blotting, ELISA, qPCR, Histology and transmission electron microscopy. We observed that YMS treatment effectively improved insulin signaling in PA-treated LO2 cells and HFD-fed mice. Notably, YMS could significantly reduce serum levels of glucose, triglycerides, fatty acids and cholesterol without affecting the serum insulin levels. Moreover, our data demonstrated that YMS could restore glucose and lipid homeostasis via facilitating insulin transportation and reactivating PI3K/Akt signaling in both PA-treated cells and liver, gastrocnemius and brown fat of HFD-fed mice. Additionally, we noticed that the therapeutic effects of YMS was similar as rosiglitazone, a well-recognized insulin sensitizer. Our findings suggested that YMS is a potentially candidate for pharmacotherapy for metabolic disorders associated with insulin resistance, particularly in T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina/fisiologia , Insulina/metabolismo , Peptídeos/farmacologia , Receptor de Insulina/farmacologia , Proteínas Recombinantes/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Nat Commun ; 9(1): 5450, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30575730

RESUMO

Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines. ADAR deletion causes activation of the double-stranded RNA sensor, protein kinase R (PKR). Disruption of PKR signaling, through inactivation of PKR or overexpression of either a wildtype or catalytically inactive mutant version of the p150 isoform of ADAR1, partially rescues cell lethality after ADAR1 loss, suggesting that both catalytic and non-enzymatic functions of ADAR1 may contribute to preventing PKR-mediated cell lethality. Together, these data nominate ADAR1 as a potential therapeutic target in a subset of cancers.


Assuntos
Adenosina Desaminase/genética , Neoplasias Pulmonares/genética , Proteínas de Ligação a RNA/genética , eIF-2 Quinase/metabolismo , Células A549 , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Helicase IFIH1 Induzida por Interferon/metabolismo , Interferons/metabolismo , Fosforilação
15.
Artigo em Inglês | MEDLINE | ID: mdl-30581488

RESUMO

Vitiligo is a kind of skin dysfunction on melanogenesis. The highly prevalent, chronic, and distinctive complexion changes on patients have imposed enormous psychic and economic burden on both individuals and society. Traditional Chinese Medicine (TCM) is a kind of precious source on chronic disease treatment, including skin dysfunctional diseases. In our previous study, a new compound named apigenin-7-butylene glucoside has been authenticated and purified from a prescription of Chinese traditional medicine formula which has been used clinically in vitiligo treatment. The aim of this work is to evaluate the effects of this compound on melanogenesis using melanoma cell B16-F10 in vitro. The results showed that apigenin-7-butylene glucoside had almost no cytotoxicity on B16-F10 cells within a lower dose of 5.0 µg ml-1 and enhanced the melanin level to about 41% and tyrosinase activity to 1.32-fold when compared with controls. The compound showed minor cytotoxicity to B16-F10 cells at the higher concentration of 10 µg ml-1 and 50 µg ml-1, the inhibition rate was 8.4% and 11.8%, and the melanin level and tyrosinase activity showed a decreased trend because of the lower cell number at the higher concentrations. The results indicated that apigenin-7-butylene glucoside was safe to B16-F10 cells within a lower concentration, <5.0 µg ml-1. Incubated with 5.0 ug ml-1of apigenin-7-butylene glucoside for 48 hours, the mRNA and protein levels of Tyr, Trp-1, and Trp-2 genes were all increased except Mitf in B16-F10 cells. The stimulation of apigenin-7-butylene glucoside on melanogenesis of B16-F10 cells through Tyr, Trp-1, and Trp-2 pathway highlighted the potential usage of the compound in vitiligo treatment.

16.
Rapid Commun Mass Spectrom ; 32(24): 2152-2158, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30252980

RESUMO

RATIONALE: Human telomeric DNA is reported to be a potential target for anticancer organometallic ruthenium(II) complexes, however, the interaction sites were not clearly discriminated and identified. METHODS: In the current study, tandem mass spectrometry (MS/MS) using collision-induced dissociation (CID) was firstly introduced to identify the interaction sites of an organometallic ruthenium(II) complex [(η6 -biphenyl)Ru(en)Cl][PF6 ] (1; en = ethylenediamine) with 5'-T1 T2 A3 G4 G5 G6 -3' (I), the repeating unit of human telomeric DNA, in both positive- and negative-ion mode at a low reaction molar ratio (1/I = 0.2) which was applied to preserve the site selectivity. RESULTS: Mass spectrometric results showed that mono-ruthenated I was the main product under the conditions. In positive-ion mode, MS/MS results indicated that ruthenium complex 1 binds to T2 or G6 in strand I. However, in negative-ion mode, no efficient information was obtained for exact identification of ruthenation sites which may be attributed to losses of fragment ions due to charge neutralization by the coordination of the positively charged ruthenium complex to the short MS/MS fragments. CONCLUSIONS: This is the first report of using top-down MS to characterize the interactions of organometallic ruthenium(II) complexes and human telomeric DNA. Thymine can be thermodynamically competitive with guanine for binding to ruthenium complexes even at low reaction molar ratio, which inspired us to explore in greater depth the significance of thymine binding.


Assuntos
Compostos Organometálicos/metabolismo , Rutênio/metabolismo , Espectrometria de Massas em Tandem/métodos , Telômero/metabolismo , Quadruplex G , Guanina/metabolismo , Humanos , Compostos Organometálicos/análise , Rutênio/análise , Telômero/química , Timina/metabolismo
17.
Fish Shellfish Immunol ; 82: 400-407, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30144566

RESUMO

A 50-day feeding trial was carried out to evaluate the partial replacement of fishmeal by yeast culture (YC) on growth performance, immune response and resistance against Aeromonas hydrophila in gibel carp CAS Ⅲ (Carassius auratus gibelio). Four isonitrogenous and isoenergetic practical diets including a basal diet (the control diet containing 10% fish meal, D0) and three yeast culture diets (substituting 20%, 40%, 60% of the fishmeal in the basal diet, D20, D40 and D60, respectively) were formulated. Each diet was randomly allocated to quadruplicate fish groups (average initial body weight: 28.70 ±â€¯0.03 g) reared in a recirculating system. After the growth trial, bacterial challenge test was conducted. The results showed that no noteworthy variations in feed intake, growth performance and morphology indices were found among groups (P > 0.05). YC Supplemented diet exerted little significant influence on plasma parameters including triglyceride, glucose, creatinine, total protein and urea nitrogen compared with the control group (P > 0.05). No obvious variations were found in activities of plasma lysozyme, IgM, MPO and SOD before challenge test among dietary treatments (P > 0.05), whereas considerable higher value of the foresaid indicators was discovered in D40 after bacteria challenge (P < 0.05). Transcriptional levels of Toll like receptor 2 (TLR2), myeloid differentiation factor 88 (MyD88), Toll/IL-1 receptor domain-containing adaptor protein (TIRAP) and interleukin-1ß (IL-1ß) in spleen after challenge were significantly up-regulated in D40 compared with D0 (P < 0.05). Cumulative survival rate in D40 and D60 were significantly higher than those in D0 and D20 (P < 0.05). Taken together, yeast culture could be a suitable fishmeal alternative in diets of gibel carp and dietary inclusion of 4 g YC per 100 g diet enhanced the immunity and disease resistance of gibel carp partly via TLR2 pathway.


Assuntos
Resistência à Doença/imunologia , Doenças dos Peixes/imunologia , Carpa Dourada/imunologia , Fermento Seco/farmacologia , Aeromonas hydrophila/fisiologia , Ração Animal/análise , Animais , Dieta/veterinária , Carpa Dourada/crescimento & desenvolvimento , Infecções por Bactérias Gram-Negativas/imunologia , Distribuição Aleatória
18.
Fish Shellfish Immunol ; 79: 265-273, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29775741

RESUMO

The present study examined the effect of dietary spirulina, Arthrospira platensis on growth performance, blood physiological indices, immune-related gene expressions and resistance of juvenile gibel carp against Aeromonas hydrophila infection. Four isonitrogenous (360 g kg-1) and isolipidic (90 g kg-1) diets were formulated with containing different levels of spirulina powder of 0 g (SP0, the control diet), 3.38 g (SP3.38), 6.76 g (SP6.76) and 13.52 g (SP13.52) per 100 g diet to replace 0%, 25%, 50% and 100% of fishmeal protein, respectively. And each diet was randomly assigned to triplicate tanks (150-L capacity per each) and each tank was stocked with 22 fish (15.37 ±â€¯0.06 g). Fish were fed one of the tested diets up to satiation twice a day for 46 days. A challenge test was carried out after the feeding trial by injecting Aeromonas hydrophila intraperitoneally for 7 days. The results showed that fish growth, feeding rate in groups SP3.38 and SP6.76 were significantly higher than those of groups SP0 and SP13.52 (P < 0.05). Feed efficiency and protein retention rate had no significant difference among all tested groups. Plasma superoxide dismutase and phagocyte activity of blood leukocytes significantly increased in the spirulina-fed fish groups at 12-h post the bacterial challenge (P < 0.05). Both pre and post challenge test, plasma lysozyme activities in spirulina-fed groups were significantly higher than that in the control group (P < 0.05). Plasma malondialdehyde got the lowest value in the SP13.52 group before and after the challenge test. The transcriptional levels of TLR2 (Toll like receptor 2), myeloid differentiation factor 88 (MyD88), Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), interleukin-1ß (IL-1ß) and tumor necrosis factor-α1 (TNF-α1) in spleen and kidney significantly increased post the bacterial challenge compared to the pre challenge. And the relative expressions of the immune-related genes of spirulina-fed fish groups were higher than those of the control group before and after the challenge test. The 7-day cumulative survival rate after the bacterial challenge was highest in the SP3.38 group (P < 0.05). The present results indicated that low dietary inclusion of spirulina significantly enhanced the immune response of gibel carp partly through TLR2 pathway and 3.38% of dietary spirulina was recommended for the juveniles based on the growth and immune response.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Regulação da Expressão Gênica/imunologia , Carpa Dourada/genética , Carpa Dourada/imunologia , Spirulina/química , Aeromonas hydrophila/fisiologia , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Resistência à Doença/imunologia , Proteínas de Peixes/metabolismo , Carpa Dourada/crescimento & desenvolvimento , Infecções por Bactérias Gram-Negativas/imunologia
19.
Cancer Cell ; 33(4): 543-544, 2018 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-29634941

RESUMO

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. In this issue of Cancer Cell, two articles by Stammnitz et al. and Frampton et al. present novel insights into the potential mechanisms underlying the propagation of naturally occurring transmissible cancers in mammals.


Assuntos
Marsupiais , Neoplasias , Animais
20.
Artigo em Inglês | MEDLINE | ID: mdl-29313521

RESUMO

Bilayer ruthenate Ca3(Ru1-xFex)2O7 (x = 0.05) exhibits an incommensurate magnetic soliton lattice driven by the Dzyaloshinskii-Moriya interaction. Here we report complex field-induced magnetic phase transitions and memory effect in this system via single-crystal neutron diffraction and magnetotransport measurements. We observe first-order incommensurate-to-commensurate magnetic transitions upon applying the magnetic field both along and perpendicular to the propagation axis of the incommensurate spin structure. Furthermore, we find that the metastable states formed upon decreasing the magnetic field depend on temperature and the applied field orientation. We suggest that the observed field-induced metastability may be ascribable to the quenched kinetics at low temperature.

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